Ineffective hematopoiesis is common in HIV infection, although the underlying mechanisms for these abnormalities are not well understood. A variety of factors, including stem cell infection, stromal cell infection with loss of satisfactory support for bone marrow growth, or cytokinetic support, may contribute. In previous studies of SIV-infected rhesus macaques, we have described peripheral blood cytopenias, stage-related CFU-GM and BFU-E hypoproliferation, absence of infection in CD34+ progenitors, and presence of an inhibitor of rhesus bone marrow secreted by HIV-infected H9 cells. These data show the similarity of SIV-infected monkeys to HIV-infected humans and suggest that ineffective hematopoiesis, with cytokinetic and inhibitory abnormalities, is a factor. The purpose of this project is to provide a comprehensive, longitudinal study of the site, function, and mechanism of the hematologic, virologic, and immunologic consequences of SIV infection in rhesus ma caques. We will delineate the currently-defined lineages of bone marrow cell types infected with SIV in highly enriched cell populations, including CD34+ and stromal cells, determine their growth potential in short- and long-term cultures, and evaluate the mechanistic roles of cellular adhesion molecules, hematopoietic cytokines, and the putative "facilitating" cell. In addition to contributing to understanding the hematologic consequences of HIV infection and their attendant morbidity, the studies proposed may also lead to a foundation for cytokine, bone marrow transplant, and gene transfer investigations. FUNDING NHLBI / R01HL53738-03 $206,552 4/01/96 - 3/31/00 PUBLICATIONS Hillyer, C.D., Lankford, K.V., Roback, J.D., Gillespie, T.W. and Silberstein, L.E. Transfusion of the HIV seropositive patient Immunomodulation, viral reactivation, and limiting exposure to EBV (HHV-4), CMV (HHV-5) and HHV-6, 7, and 8. Transfusion Med Rev (In press). P51RR00165-38 1/1/1998 - 12/31/1998 Yerkes Regional Primate Research Center